Human papillomavirus type 16 E6 and E7 cause polyploidy in human keratinocytes and up-regulation of G2-M-Phase proteins

Human papillomavirus type 16 proteins E6 and E7 have been shown to cause centrosome amplification and lagging chromosomes during mitosis. These abnormalities during mitosis can result in missegregation of the chromosomes, leading to chromosomal instability. Genomic instability is thought to be an es...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-02, Vol.64 (4), p.1299-1306
Main Authors: PATEL, Daksha, INCASSATI, Angela, WANG, Nancy, MCCANCE, Dennis J
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Cell Cycle Proteins
Cell Line
G2 Phase
Gene Expression Regulation
Humans
Keratinocytes - ultrastructure
Medical sciences
Mitosis
Nocodazole - pharmacology
Oligonucleotide Array Sequence Analysis
Oncogene Proteins, Viral - physiology
Papillomavirus E7 Proteins
Pharmacology. Drug treatments
Polo-Like Kinase 1
Polyploidy
Protein Kinases - biosynthesis
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins
Repressor Proteins
Retinoblastoma Protein - physiology
Tumor Suppressor Protein p53 - metabolism
Tumors
Up-Regulation
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Summary:Human papillomavirus type 16 proteins E6 and E7 have been shown to cause centrosome amplification and lagging chromosomes during mitosis. These abnormalities during mitosis can result in missegregation of the chromosomes, leading to chromosomal instability. Genomic instability is thought to be an essential part of the conversion of a normal cell to a cancer cell. We now show that E6 and E7 together cause polyploidy in primary human keratinocytes soon after these genes are introduced into the cells. Polyploidy seems to result from a spindle checkpoint failure arising from abrogation of the normal functions of p53 and retinoblastoma family members by E6 and E7, respectively. In addition, E6 and E7 cause deregulation of cellular genes such as Plk1, Aurora-A, cdk1, and Nek2, which are known to control the G(2)-M-phase transition and the ordered progression through mitosis.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-03-2917